Triamine acid addition salts of caprylic, propionic and undecylenic acids



United States Patent 3,164,619 TRIAMENE ACID ADDITION SALTS OF CAPRYLIC, PRGPIQNIC AND UNDEtIYLENIC ACIDS Michael G. Mulinos, Westiield, N .11., assignor to Commercial Solvents Corporation, a corporation of Maryland No Drawing. Filed Sept. 19, 1960, Ser. No. 56,661 9 Claims. (Cl. 260404.5)

My invention relates to alkyl triamines and more particularly it relates to acid addition salts of alkyl triamines which salts possess antifungal activity.

US. Patent 2,436,779 by Murray Senkus describes certain alkyl triamines including some of the compounds from which my new acid addition salts are prepared. Similarly copending application Serial No. 738,928 filed June 2, 1958, now abandoned, by John B. Tindall describes applicable alkyl triamines.

In the past many compounds have been discovered to have antibacterial activity, but comparatively few have been found to have antifungal activity permitting therapeutic use at practical levels. Further consideration must also be given to toxicity, especially the topical irritation and skin sensitization (allergenicity) frequently encountered in the use of prior antifun gal agents.

I have now discovered new compositions possessing practical antifungal activity which new compositions are essentially non toxic when employed in amounts adequate to eradicate fungal infections caused by susceptible fungi.

The new triamine acid addition salts of my invention have the following general formula:

wherein R consists of groups selected from the class consisting of hydrogen and methyl, with the proviso that if one R is methyl, then the other R must be hydrogen; R consists of groups selected from the class consisting of caprylic, propionic or undecylenic acids, and x is either 0 or 1, with the proviso that at least one x is 1.

Illustrative of compounds included in the above general formula are N ,2-dimethyl-N ,N -bis(2-ethylhexyl)-1,2,3-propanetriamine mono-propionate,

N ,2-dimethyl-N ,N -bis (Z-ethylhexyl) -1,2,3-

propanetriarnine dipropionate,

N ,2-dimethyl-N ,N -bis(2-ethylhexyl) -1,2,3-

propanetriarnine tripropianate,

N ,2-dimethyl-N ,N -bis (Z-ethylhexyl) -1,2,3-

propanetriamine monocaprylate,

N ,2-dimethyl-N ,N -bis (2-ethylhexyl) -1,2,3-

propanetriamine dicaprylate,

N ,2-dimethyl-N ,N -bis (2-ethylhexyl)-l,2,3-

propanetriamine tricaprylate,

N ,2-dimetliyl-N ,N -bis(Z-ethylhexyl) -l,2,3-

propanetriamine mono-undecylenate,

N ,2-dimethyl-N ,N -bis (2-ethylhexyl) -1,2,3

propanetriamine diundecylenate,

N ,2-dimethyl-N ,N -bis (2-ethylhexyl)-1,2,3- propanetriamine triundecylenate,

N ,N -bis(2-ethylhexyl)-2-methyl-1,2,3-propanetriamin mono-propionate,

N ,N -'bis (2-ethylhexyl) -2-methyl-1,2,3-propanetriamine dipropionate,

N ,N -bis (Z-ethylhexyl) -2-methyl- 1,2,3 -prop anetriarnine tripropionate,

N ,N -bis (Z-ethylhexyl) -2-methyl-l,2,3 -propanetriamine mono-caprylate,

N ,N -bis(2-ethylhexyl)-2-methyl-l,2,3-propanetriamine dicaprylate,

of my invention is in the form of an aerosol.

3,164,619 Patented Jan. 5, 1965 N ,N -bis(2-ethylhexyl)-2-methyl-1,2,3-propanetriamine tricaprylate, N ,N -bis(2-ethy1hexyl)-2-methyl-1,2,3-prop'anetriamine mono-undecylenate, N ,N -bis (Z-ethylhexyl -2-methyl- 1,2,3 -prop anetriamine diundecylenate, N ,N -bis(2-ethylhexy1)-2-methyl-1,2,3-propanetriamine triundecylenate and the like.

In preparing the triamine acid addition salts of my invention, I utilize the corresponding triamine. The corresponding triamines have the following general formula:

wherein R consists of groups selected from the class consisting of hydrogen andmethyl with the proviso that if one R is methyl, then the other R must be hydrogen. The selected triamine is then reacted with propionic, caprylic or undecylenic acids.

The triamine acid addition salts of my invention are prepared by mixing 1 mole of the corresponding triamine with 1, 2, or 3 moles of caprylic, propionic or undecylenic acid. Furthermore, mixtures of the three acids can be used. For instance, I can mix 1 mole of N ,N -bis(2 ethylhexyl)-2-methyl-l,2,3-propanctriamine with 1 mole of caprylic and '2 moles of undecylenic acids, or I can mix 1 mole of N ,N -bis(Z-ethylhexyl)-2-methyl-l,2,3- propanetriamine with 2 moles of propionic acid, etc.

When utilizing N ,2-dimethyl-N ,N -bis(2-ethylhexyl)- 1,2,3-propanetriamine, as the triamine starting material, it can be prepared according to the disclosure of copending application Serial No. 738,928 filed June 2, 1958 by John B. Tindall.

. Whereas, when utilizing N ,N -bis(2-ethylheXyl)-2- methyl-1,2,3-propanetriamine, as the triamine starting material, it can be prepared according to the disclosure of US. Patent No. 2,43 6,779.

The new compounds of my invention are uniquely suited for use as antifungal agents. For example, they can be incorporated in soaps and other suitable vehicles to enhance the normal washing activity of soaps with antifungal properties. My new compounds can also be used in shampoos to give antifungal properties to shampoos and thereby give antifungal protection to those areas or objects washed with these cleansers.

A therapeutic antifungal foot powder can be prepared by mixing 0.5 to 5.0 grams of N ,2-dimethyl-N ,N -bis- (2-ethylhexyl)-l,2,3-propanetrian1ine tricaprylate with 10.0 grams boric acid, 20.0 grams of starch and enough talc to make a 100.0 gram composition.

Similarly my compounds can be used to impart antifungal activity to ointments and lotions. For instance a very fine washable therapeutic ointment can be prepared by mixing 0.5 to 5.0 grams of N ,2-dimethyl-N ,N bis(2-ethylhexyl)-1,2,3 propanetriamine tripropionate with enough hydrophilic ointment (U.S.P.) to make grams of ointment.

Furthermore a nonwater washable therapeutic ointment can be prepared by mixing 0.5 to 5.0 grams of N ,N -bis(2-ethylhexyl)r1,2,3-propanetriarnine diundecylenate with enough white ointment (U.S.P.) to make 100 grams of ointment.

Another excellent way to apply the novel compositions Aerosols provide a good carrier and efiicient mode of application for topical therapy in the treatment of superficial fungous infections.

The following table sets out the antifungal effects of some of the novel compounds of my invention. The

sneaeia compounds set out in Table I were found to inhibit completely the described organism at the described minimum inhibition concentration.

, a 7.4 grams of propionic acid and the resulting compound was N ,2-dimethyl-N ,N -bis(2-ethylhexyl) 1,2,3-pr0- panetriarnine mono-propionate.

TABLE I Minimum Inhibitory Concentrations in Parts per Million Test; Organism Test Compound Aspargillus Candida Penicillium Fusarium niger albicans chrysogenum ozyspomm N ,2-dimethy1-N ,N -bis(Z-ethylhexyl)-1,2,3-proanetriamifle dipr pi nate 500-100 500-1, 000 1 10.100

pan am p opi te 100-500 100-500 100-500 10400 N ,2-dimethyl-N ,N -bis(Z-ethylhexyl)-1,2,3-propanetriarnine dicaprylate 500-1, 000 500-1, 000 100-500 10400 N ,2-dimethyl-N ,N -bis(2-ethylhexyl)-1,2,3-proanetriarnine tricaprylate 100-500 100-500 1 10400 N ,N -bis(2-ethy1hexyl)-2-methy1-1,2,3-propanetriamine dipropionate 100-500 100-500 1 -1 10400 N ,N -bis(2-ethylhexyl)-2-methyl-1,2,3-propanet amine tripropionatei 131.13 100-500 100-500 10-100 10-100 N N -bis Z-eth lhexy -2-me' y propane riamine d icapr r late 5.". 100-500 100-500 10-10 10.100 N N -bs Z-eth lhex l -2-rnethyl-1 2 3-propane ridmine tiicapr late 1.. 100-500 100-500 10400 1.0400

The following examples further illustrate my invention, but it is not intended that my invention be limitedto the compounds, etc., set out therein. Rather, it is intended that equivalents obvious to those skilled in the art be included within the scope of my invention as claimed.

EXAMPLE I To a beaker containing 32.7 grams of N ,2-dimethyl- N ,N -bis(2-ethylhexyl) 1,2,3-propane triarnine were added-22.2 grams of propionic acid. The mixture was thoroughly stirred and left standing until the heat of reaction hadsubsided. The resulting compound was N ,2- dimethyl-N ,N -bis(2-ethylhexyl) 1,2,3-propanetriamine tripropionate.

EXAMPLE II 34.1 grams of N ,N -bis(2-ethylhexyl)-2-methyl-1,2,3- propanetriamine were treated as in Example I with 28.8 grams of caprylic acid and the resulting compound was N ,N -bis(2-ethylhexyl)-2-methyl 1,2,3-propanetriamine dicaprylated.

EXAMPLE III 32.7 grams of N ,2-dimethyl-N ,N -bis(2-ethylhexyl)- 1,2,3-propanetriamine were treated as in Example I with 18.4 grams of undecylenic acid and the resulting compound was N ,2-dimethyl-N ,N -bis(2-ethylhexyl)-1,2,3- propanetriarnine mono-undecylenate.

7 EXAMPLE IV V 34.1 grams of I-l ,N -bis(2-ethy1hexyl)-2rnethyl-1,2,3- propanetriamine were treated as in Example I with 14.8 grams of propionic acid and the resulting compound was N ,N -bis(2-ethy1l1exyl) 2-rnethyl-1,2;3-propanetriamiue dipropionate.

EXAMPLE V 32.7 grams of N ,2-dimethyl-N ,N -bis(2-ethylhexyl)- 1,2,3-propanetriamine were treated as in Example I with 43.3 grams of caprylic acid and the resulting compound was N ,2-dimethy1 N ,N bis(2-ethylhexyl) 1,2,3-propanetriamine tricapryl-ate.

EXAMPLE VI 34.1 grams of N ,N -bis(2-ethylhexyl)-2-methyl-1,2,3- propanetriamine were treated as in Example I with 18.4 grams of undecylenic acid and the resulting'compound was N ,N -bis(2-ethylhexyl) 2-methyl-1,2,3-propauetria- EXAMPLE VIII 34.1 grams of N ,N -bis(2-ethylhexyl)-2-rnethyl-l,2,3- propanetriamine were treated as in Example I with 14.4 grams of caprylic acid and the resulting compound was N ,N -bis(2-ethylhexy1) Z-methyl-1,2,3-propanetriamine mono-caprylate.

EXAMPLE IX 32.7 grams of N ,2-dimethyl-N ,N -bis(Z-ethylhexyl)- 1,2,3-pr0panetriamine were treated as in Example I with 36.9 grams of undecylenic acid and the resulting compound was N ,2-dirnethyl-N ,N -bis(Z-ethylhexyl)-l,2,3- propanetriamine diundecylenate.

EXAMPLE X 34.1 grams of N ,N -bis(Z-ethylhexyl)-2-methyl-1,2,3- propanetriamine were treated as in Example I with 55.3 grams of undecylenic acid and the resulting compound was N ,N -bis(2-ethylhexyl) Z-methyl-l,2,3-propanetriamine triundecylenate.

EXAMPLE XI 32.7 grams of N ,2-dimethyl-N ,N -bis(2-ethylhexyl)- 1,2,3-propanetriamine were treated as in Example I with 14.8 grams of propionic acid and the resulting compound was N ,2 dimethyl N ,N -bis(2-ethy1hexyl) 1,2,3-propanetriamine dipropionate.

EXAMPLE XII.

34.1 grams of N ,N -bis(2-ethylhexyl)-2-methyl-1,2,3- propanetriamine were treated as in Example I with 43.3 grams of cap rylic acid and the resulting compound was N ,N bis(2-ethylhexyl)-2-methyl-1,2,3-p-ropanetriamine tricaprylate.

EXAMPLE XIII 32.7 grams of N ,2-dimethyl-N ,N -bis(Zethylhexyl)- 1,2,3-propanetriamine were treated as in Example'I with 14.4 grams of caprylic acid and the resulting compound was N ,2-dimethy1-N ,N -bis (Z-ethylhexyl) -1,2,3 -propanetriamine mono-caprylate.

EXAMPLE XIV 34.1 grams of N ,N -bis(2-ethylhexyl)-2-methyl-1,2,3- propanetriamine were treated as in Example I with 7.4 grams of propionic acid and the resulting compound was N ,N bis(2-etl1ylhexyl)-2-methyl-1,2,3-propanetriamine mono-propionate.

. EXAMPLE XV 32.7 grams of N ,2-dimethyl-N ,N -bis(Z-ethylhexyl)- 1,2,3-propanetriamine were treated as in Example I with 55.3 grams of undecylenic acid and the resulting compound was N ,2-dimethyl-N ,N -bis(2-ethylhexyl)-1,2,3-

propanetriamine triundecylenate.

EXAMPLE XVI 34.1 grams of N ,N -bis(2-ethy1hexyl)-2-methyl-1,2,3- propanetriamine were treated as in Example I with 22.2 grams of propionic acid and the resulting compound was N ,N bis(2-ethylhexyl)-2-methyl-1,2,3-propanetriamine tripropionate. 5

EXAMPLE XVII 32.7 grams of N ,2-dimethyl-N ,N -bis(2-ethylhexyl)- 1,2,3-pr0panetriamine were treated as in Example I with 28.8 grams of caprylic acid and the resulting compound was N ,2-dimethy1-N ,N -bis(2-ethylhexy1-1,2,3-propanetriamine dicaprylate.

EXAMPLE XVIII 34.1 grams of N ,N -bis(2-ethylhexy)-2 methy1-1',2,3- propanetriamine were treated as in Example Iwith 36.9 grams of undecylenic acid and the resulting compound Was N ,N -bis (2-ethylhexyl -2-methyl-1,2,3-propanetriamine diundecylenate.

Now having described my invention, what I claim is:

1. As a composition of matter, triamine acid salts having the following formula:

wherein R represents a member selected from the group consisting of hydrogen and methyl, with the proviso that if one R is methyl then the other R must be hydrogen; and

R represents a member selected from the group consisting of caprylic, propionic and undecylenic acids, and x is selected from the class consisting of 0 and 1, with the proviso that a least one x is 1.

2. N ,2 dimethyl N ,N -bis(2-ethylhexyl)-1,2,3-propanetriamine mono-propionate.

3. N ,N bis(2-ethylhexyl)-2-methyl-1,2,3-propanetriamine tripropionate.

4. N ,2-dimethyl N ,N bis(2-ethylhexyl)-1,2,3-propanetriamine dicaprylate.

5. N ,N bis(2-ethylhexyl)-2-methyl-1,2,3-propanetriamine tricaprylate.

6. N ,N bis (Z-ethylhexyl) -2-methy1-1,2,3-pr0panetriamine triundecylenate.

7. The composition of claim 1 wherein R is caprylic acid.

8. The composition of claim 1 wherein R is propionic acid.

9. The composition of claim 1 wherein R is undecylenic acid.

References Cited in the file of this patent UNITED STATES PATENTS 2,290,174 Epstein et al. July 21, 1942 2,436,779 Senkus Feb. 24, 1948 2,994,765 Haward et al. Aug. 1, 1961 2,998,438 Charney et al Aug. 29, 1961 OTHER REFERENCES Richter: Textbook of Organic Chemistry, pages 245 and 246, third edition, 1952, John Wiley and Sons, Inc., New York. 

1. AS A COMPOSITION OF MATTER, TRIAMINE ACID SALTS HAVING THE FOLLOWING FORMULA: 